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Demyelinating disorders in central nerve system

Demyelinating disorders in central nerve system. Myelin in CNS is formed by the oligodendrocytes. Chemical composition: proteolipid, myelin basic protein, 2’-3’ cyclic nucleotide phosphohydrolase, myelin-associated glyco-protein,

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Demyelinating disorders in central nerve system

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  1. Demyelinating disorders in central nerve system

  2. Myelin in CNS is formed by the oligodendrocytes Chemical composition: proteolipid, myelin basic protein, 2’-3’ cyclic nucleotide phosphohydrolase, myelin-associated glyco-protein, myelin-oligodendrocyte glyco-protein.

  3. Intact myelin is required for action potential conduction

  4. Myelined nerve fiber are rich in white matter of cerebral 、cerebella、brain stem、spinal cord，optic nerve

  5. Demyelinating —— myelin is broken, axon remains intact

  6. Multiple Sclerosis(MS) 1 Neuromyelitis optica (NMO) 2 Acute Disseminated Encephalomyelitis (ADEM) 3 Concentric sclerosis(Balo’s disease) 4 Inflammatory demyelinating disorders in central nerve system

  7. Inflammatory demyelinating disorders In CNS Multiple Sclerosis (MS)

  8. What is Multiple Sclerosis? Multiple Sclerosis (MS) • “sclerosis” comes from the Greek word “skleros”, meaning hard. In multiple sclerosis, hard areas called “plaques” . • “Multiple” refers to the many different areas of the nervous system that may have damaged myelin.

  9. What is Multiple Sclerosis ? • chronic inflammatory disease of CNS • malfunction of the immune system which leads to attacks against myelin sheath • insulating myelin is damaged. • The loss of myelin insulation degrades the nerve transmission ability. • Thus a multitude of various neurological disabilities can be observed in patients affected by this disease depending on which nerves are damaged.

  10. Epidemiology approximately 1.1 million people are affected in US in all parts of the world and in all races, but whites of northern European descent have the highest incidence. occur in any age. usually diagnosed in aged 15-45 years; average age at diagnosis is 29 years in women and 31 years in men. female to male ratio is 2:1.

  11. symptoms • MS was first described by Cruveilhier in 1835. • A generally valid description of MS symptoms was made by Charcot in the year 1868. • In 1904 the description was supplemented by Müller.

  12. Multifocal lesions

  13. Multifocal lesions

  14. Common symptoms: Sensory disturbance Weakness Problems in walking/balance/ coordination Visual problems： optic nerve Other possible symptoms: Bladder problem Spasticity Fatigue Facial weakness Trigeminal neuralgia slurred speech trouble swallowing Deafness temporary blindness Cognitive problems Epilepsy Depression symptoms

  15. signs • Local weakness • Local sensory disturbances • poor coordination of upper and lower extremity movements, wide-based gait with inability to tandem walk. • nystagmus, internuclearophthalmoplegia, • visual disturbances, pallor of the optic disc, • Lhermitte sign, traverse spinalmyelopathy，Brown-sequardsyndrome in different levels of spinal cord

  16. Courses (multiple phases)

  17. Laboratory findings • Magnetic Resonance Imaging (MRI) will show patches of tissue • CSF：WBC，protein，MBP，OB， specific Abs • Evoked Potentials： visual evoked potentials（VEP） auditory evoked potentials（BAEP） somatosensory evoked potentials（SEP）

  18. How is multiple sclerosis diagnosed? • Time——mutiple phases • Space—— mutifocal lesions • Exclude others

  19. The Diagnostic Criteriaof MS （Poser, 1983 ) Evidence of More Than One Lesion CSF OCB or IgG Number of Attack Clinical Lab. A. Clinically Definite A1 2 2 A2 2 1 and 1 B. Lab-Supported Definite B1 2 1 or 1 + B2 1 2 + B3 1 1 and 1 + C. Clinically Probable C1 2 1 C2 1 2 C3 1 1 and 1 D. Lab-Supported Probable D1 2 0 0 +

  20. Diagnostic Criteria for Multiple Sclerosis (McDonald Criteria，2001）（1）

  21. Diagnostic Criteria for Multiple Sclerosis (McDonald Criteria，2001）(2)

  22. Differential diagnosis • First attack: single lesion or multiple lesions: infection, tumor, infarction, • Relapse type: infarction, embolism, vasculitis, • Progressive: inherited, degenerating,

  23. Pathology of MS • Gross neuropathology grey plaques (acute plaque may be pink) may occur anywhere • Microscopic neuropathology perivascular lymphocytes infiltrate; loss of oligodendrocytes; myelin stripping; macrophage infiltrate; astrogliosis; relative sparing of axons

  24. The exact cause of MS is not known Environmental Factors： Geography is clearly an important factor the rate is approximately twice as below the 37th parallel. Genetic Factors： MS is not strictly an inherited disorder. Susceptibility to MS probably has a genetic component. What Causes MS?

  25. Pathogenesis of MS:incompletely understood. • Immune-mediated disorderwith aninitial trigger • Molecular mimicry • Oligodendrocyte susceptible • CNS infections may also lead to the transmigration of activated T lymphocytes into the CNS, which initiate the process

  26. How is MS Treated? Immunotherapy • Corticosteroids corticosteroids can reduce the duration of symptoms, they do not cure MS. Used in Acute attacksintravenous methylprednisolone 1000 mg daily for three days. Prednisone: Clinicians differ on whether to taper off treatment with oral prednisone for two weeks, but this probably does not improve results and increases side effects.

  27. Interferons Beta interferon drugs have shown to be effective in treating the relapsing-remitting type of MS.

  28. Immunosuppressants methotrexate, cyclophosphamide, cyclosporine, mitoxantrone. Others IvIg plasma exchange

  29. Symptomatic management Bladder frequency and urgency will often respond to oxybutynin. Pain and spasms from spastic limbs usually respond to baclofen. Emotional lability with pathological laughing or crying can be managed with a tricyclic antidepressant. Amantadine reduces fatigue in half the patients. More difficult to manage are pain, sexual dysfunction, weakness, dysesthesia and other sensory symptoms, tremor, ataxia, and cognitive change, but even these may respond to various therapeutic approaches. It is important to recognise that half of patients with multiple sclerosis will become depressed and that therapy and counselling may be necessary.

  30. Prognosis • Mortality/Morbidity: Life expectancy is shortened only slightly with MS, and the survival rate is linked to disability. Usually, death is due to secondary complications (50-66%), such as pulmonary or renal causes, suicide, primary complications, and causes other than MS seen in the general population.

  31. Inflammatory demyelinating disorders in CNS Neuromyelitis optica (NMO)

  32. Similarities with MS • mutifocal lesions • mutiple phases • immuno-mediated inflammatory demyelinationin CNS

  33. DifferenceswithMS----mutifocal lesions • Myelitis：longlesion ≧ 3 vertebral segments. • Optis neuritis： • Brain lesions：atypical for MS. • Multiple phases：more frequently a relapsing-remittingcourse.

  34. Optic nerve atrophy

  35. DifferenceswithMS ----Pathological featuresofNMO • demyelination and necrosis • prominent vascular fibrosis and hyalinization within the lesions • perivascular deposition of IgG and complement • perivascular infiltrates of polymorphonuclear cells, leucocytes , plasma cells,eosinophils • glial scars are less frequent and usually only partial in contrast to typical MS lesions

  36. DifferenceswithMS ----pathogenesis of NMO • humoral immunity • target antigen is aquaporin-4, the dominant water channel in (CNS) • IgG-antibody to aquaporin-4, named NMO-IgG

  37. Diagnositiccriteria for NMO

  38. Differential diagnosis • Ischemia of optic nerve • Acute myelitis • Vascular disease of the spinal cord • Vasculitis • Connective tissue disease

  39. DifferenceswithMS----Treatment • acute phase：intravenous steroids and plasma exchange therapy. • To prevent relapse：oral steroid medication and immunosuppressive drugs.

  40. Inflammatory demyelinating disorders in CNS Acute Disseminated Encephalomyelitis (ADEM)

  41. Acute Disseminated Encephalomyelitis • Quite rapid in onset, often getting sick over a period of a few days • Multifocal neurological dysfunction, involving brain、spinal cord、 meninges • MRI： multifocal lesions in CNS • CSF：WBC count normal or mild elevated , immune proteins level elevated • Good response to therapy ：corticosteroid treatments • Precipitating Events：recent infections and certain recent vaccinations，certain medications, trauma, idiopathic   • Most ADEM are monophasic ， some are MDEM（multiphasic Disseminated Encephalomyelitis), or develop to MS

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